Sargramostim for Myeloid Dendritic Cell Deficiency

Kidney Diseases Clinical Trial

Official title:

Sargramostim to Reverse Myeloid Dendritic Cell Deficiency

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03063242
• Other study ID #: IRB201600815
• Secondary ID: OCR16461
• Status: Terminated
• Phase: Phase 2
• Start date: February 23, 2017
• Est. completion date: September 17, 2018

Study information

• Verified date: December 2018
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will determine whether administration of sargramostim will improve myeloid dendritic cell deficiency in various study groups, including healthy subjects and patients with chronic kidney disease, including those with kidney transplants.

Description:

The overall objective of this project is to study the ability of sargramostim to enhance mDC level and function, including subsequent stimulation of T cell responses, in various human subjects with demonstrated myeloid dendritic cell (mDC) and T cell deficiency.

Single center nonrandomized trial with an interrupted time series design involving measures on blood samples from three separate populations before and after administration of sargramostim.

The objective is to determine the safety and dose response of sargramostim administration in healthy participants and in patients with chronic kidney disease (CKD) and kidney transplants.

Additionally to determine whether reversal of mDC/T cell deficiency by sargramostim results in augmented T cell responses in these three groups.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 17, 2018
• Est. primary completion date: September 17, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age >18 years < 80 years

• Absence of acute or chronic medical condition and taking no prescription medications (Project I)

• Stable native or transplant kidney function (Project II/III)

Exclusion Criteria:

• Age < 18 or > 80 years

• History of non-adherence to prescribed medications (Projects II and III)

• Active drug or heavy alcohol use (defined as > 4 drinks/day)

• Pregnancy or breast feeding

• Active infection (bacterial or viral) or clinically significant infections within the past three months (e.g. those requiring hospitalization, or as judged by the PI, except for CMV viremia in Project III)

• Active malignancy (with the exception of excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or adequately treated pre-invasive cervical cancer in situ)

• Unstable cardiovascular status (angina, arrhythmias, congestive heart failure (CHF) etc…)

• History of liver disease (as defined by a diagnosis of uncompensated cirrhosis)

• History of lung disease (including moderate-severe Chronic Obstructive Pulmonary Disease (COPD), interstitial lung disease, or asthma)

• Known hypersensitivity to yeast-derived products

• Hemoglobin < 10 g/dL and hematocrit < 30%.

• Abnormal white blood cell count (WBC) count at baseline (< 3 or > 12 x 103 cells/mm3, except Project III)

• Treatment with WBC growth factors (G-CSF or GM-CSF) or immunosuppressive medications (tacrolimus, cyclosporine, mycophenolate, azathioprine, corticosteroids, chlorambucil, cyclophosphamide) within 4 weeks of study (erythropoiesis-stimulating agents will be allowed for Project II and immunosuppression for Project III)

• Treatment with lithium within 4 weeks of study

• History of arterial or venous thrombosis

Related Conditions & MeSH terms

• Kidney Diseases
• Kidney Transplant

Intervention

Drug:
• Sargramostim
Study participants (n=5 per project) will receive subcutaneous injection of sargramostim (6 ug/kg) daily until maximal mDC levels are achieved, as determined by a dose response curve.

Biological:
• Blood samples
Blood samples will be drawn at baseline and during each subsequent visit

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peripheral blood mDC levels	mDC levels to >2.0 x104 mDCs/mL, with the target level defined as levels at or above upper quartile values in healthy controls	Baseline to 2 weeks
Secondary	Proportion of patients with adverse events during the intervention.		Baseline to 2 weeks
Secondary	Increase in T cell levels, mDC Interleukin (IL)-12 production, and interferon-gamma (IFN-y) production in QuantiFERON-CMV and QuantiFERON-Monitor assays after the intervention.		Baseline to 2 weeks